Comparative genomic hybridization (CGH) was used to screen for changes in the number of DNA sequence copies in 30 primary colorectal cancers and 16 liver metastases, to identify regions that contain genes important for the development and progression of colorectal cancer. In primary colorectal cancer, we found frequent gains at 7p21 (36.7%), 7q31-36 (30%), 8q23-24 (43.0%), 12p (30%) Many detailed reports have been published on the carcinogenesis of colorectal cancer. Several genetic aberrations are required for tumor initiation and progression. 1 These aberrations include activation of the SRC and RAS oncogenes 2,3 along with inactivation of the FAP 4,5 and DCC 6 tumor suppressors and loss of TP53 function. 7 However, genetic changes involved in the progression and metastases of colorectal cancer remain unclear. To investigate differences in chromosomal aberrations between primary colorectal cancer and metastatic liver tumor, we used comparative genomic hybridization (CGH). CGH is based on dual-color fluorescence in situ hybridization (FISH) using differentially labeled tumors and reference DNA as a probe. 8,9 The efficacy of CGH is based on the concept that regions with an increase in the number of copies reveal sites that may contain dominantly acting oncogenes, whereas regions with a reduction may harbor putative tumorsuppressor genes. 8 Our aim was to generate a comprehensive picture of genomic and chromosomal aberrations that occur during the development of metastases of colorectal cancers and to identify those chromosomal regions that contain genes important for the development and progression of colorectal cancer.,Colorectal adenoma and adenocarcinoma have previously been analyzed by CGH, 10 as have primary and metastatic liver tumors. 11,12 These results supported ours; above all, we emphasize that some important genes appear to be contained in 20q and to play an important role in liver metastases. Furthermore, we examined the follow-up surveys of all cases and compared cases with and without loss at 18q and with gains at 8q and 20q to determine the usefulness of these genetic alterations as prognostic markers. MATERIAL AND METHODS Samples and DNA preparationPrimary tumors and metastatic liver tumors from 44 cancer patients with colorectal cancer (Table I) were classified according to the UICC system. These samples were provided by the Department of Digestive Surgery, Kyoto Prefectural University of Medicine (Kyoto, Japan). After surgical resection, tissues were frozen and stored at -80°C and DNA was extracted. CGHCGH was performed as described previously. 13 In brief, tumor DNA was labeled with FITC-dUTP and controlled DNA and extracted from a normal male with the aid of Texas red-dUTP using nick translation. Metaphase spreads were denatured at 75°C for 2.1 min in a formamide solution [70% formamide, 2 ϫ SCC (pH 7.0)] and dehydrated in an ethanol series of 70%, 85% and 100%. Labeled tumor and normal DNAs together with 10 g unlabeled cot-1 DNA was mixed with 50% formamide, 10% dextran sulfate and 2 ϫ SSC...
Guideline-based parenteral hydration therapy contributed to maintaining global QoL and provided satisfaction and a feeling of benefit without increasing discomfort and worsening symptoms and fluid retention signs in patients with advanced cancer.
Background Most advanced elderly cancer patients experience fatigue, anorexia, and declining physical function due to cancer cachexia, for which effective interventions have not been established. We performed a phase I study of a new nonpharmacological multimodal intervention called the nutritional and exercise treatment for advanced cancer (NEXTAC) program and reported the excellent feasibility of and compliance with this program in elderly patients with advanced cancer who were at risk for cancer cachexia. We report here the background, hypothesis, and design of the next-step multicenter, randomized phase II study to evaluate the efficacy of the program, the NEXTAC-TWO study. Methods Patients with chemo-naïve advanced non-small cell lung cancer or pancreatic cancer, age ≥ 70 years, performance status ≤2, with adequate organ function and without disability according to the modified Katz index will be eligible. In total, 130 participants will be recruited from 15 Japanese institutions and will be randomized into either the intervention group or a control group. Computer-generated random numbers are allocated to each participant. Stratification factors include performance status (0 to 1 vs. 2), site of primary cancer (lung vs. pancreas), stage (III vs. IV), and type of chemotherapy (cytotoxic vs. others). Interventions and assessment will be performed 4 times every 4 ± 2 weeks from the date of randomization. Interventions will consist of nutritional counseling, nutritional supplements (rich in branched-chain amino acids), and a home-based exercise program. The exercise program will include low-intensity daily muscle training and lifestyle education to promote physical activity. The primary endpoint is disability-free survival. It is defined as the period from the date of randomization to the date of developing disability or death due to any cause. This trial also plans to evaluate the improvements in nutritional status, physical condition, quality of life, activities of daily living, overall survival, and safety as secondary endpoints. Enrollment began in August 2017. The study results will demonstrate the efficacy of multimodal interventions for elderly cancer patients and their application for the maintenance of physical and nutritional conditions in patients with cancer cachexia. This work is supported by a grant-in-aid from the Japan Agency for Medical Research and Development. Discussion This is the first randomized trial to evaluate the efficacy and safety of a multimodal intervention specific for elderly patients with advanced cancer. Trial registration Registered at August 23, 2017. Registry number: UMIN000028801 . Electronic supplementary material The online version of this article (10.1186/s12885-019-5762-6) contains supplementary material, which is available to authorized users.
prognosis of advanced gastric cancer is still poor, chemotherapies were reported to improve the overall survival compared to the best supportive care in several studies [2][3][4]. Among the various active chemotherapeutic agents, cisplatin-based chemotherapy is the most commonly used worldwide. The V-325 study demonstrated that adding docetaxel (D) to a frequently used regimen of cisplatin and 5-fl uorouracil (CF) provided benefi ts with regard to overall survival, response rate, time to disease progression, clinical benefi t, and healthrelated quality of life [5]. Although the DCF regimen provides these advantages, it is accompanied by an increase in toxicity compared with the doublet regimen. The toxicity profi le of DCF is acceptable only with appropriately selected patients and comprehensive toxicity management strategies [6]. In this regard, the development of less toxic new combination chemotherapy has still been considered necessary to properly treat those patients with advanced gastric cancer.Paclitaxel, (Taxol; Bristol-Myers Squibb, Princeton, NJ, USA), which is derived from the bark of the Pacifi c yew, Taxus brevifolia, is one of the most active anticancer drugs for the treatment of solid tumors, effectively blocking cancer cells in the G2/M phase through the inhibition of microtubular depolymerization [7,8]. An administration schedule at doses of 175-225 mg/m 2 by intravenous infusion every 3 weeks has been widely accepted [9]. In addition, several phase II studies have shown that paclitaxel, alone or in combination with cisplatin or 5-fl uorouracil (5-FU), is also active against advanced gastric cancer [10-13]. However, a relatively high incidence of grade 3 or 4 neutropenia (14%-35%) is one of the major adverse effects.Paclitaxel is known to be a cell-cycle-specifi c agent, and in vitro experiments have suggested that prolonged Results. A total of 54 patients were registered. All of them had measurable disease and were determined to be eligible for the present study. Two complete responses and 23 partial responses were confi rmed, giving an overall response rate of 46.3%. At a fi nal follow up of 3 years, the median progressionfree survival and median overall survival were 6.0 and 14.3 months, respectively. Grade 3 neutropenia occurred in 14 patients, and grade 4 in 1 patient (total, 27.8%). The most serious nonhematological toxicity was diarrhea, where grade 3 occurred in 5 patients (9.3%). There were no treatmentrelated deaths. Conclusion. A combination of weekly paclitaxel plus S-1 was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation with comparative trials is needed for confi rmation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.